Related Experiment Video

Updated: Feb 28, 2026

Comet Assay to Quantify DNA Damage in FLT3 Mutant-expressing 32D Cells after Exposure to Type I and Type II FLT3 Inhibitors
04:36

Comet Assay to Quantify DNA Damage in FLT3 Mutant-expressing 32D Cells after Exposure to Type I and Type II FLT3 Inhibitors

Published on: October 17, 2025

1.0K

The MET/AXL/FGFR Inhibitor S49076 Impairs Aurora B Activity and Improves the Antitumor Efficacy of Radiotherapy

Céline Clémenson1,2, Cyrus Chargari1,2,3,4, Winchygn Liu1,2

  • 1Gustave Roussy, Université Paris-Saclay, UMR Radiothérapie Moléculaire, Villejuif, France.

Molecular Cancer Therapeutics
|June 17, 2017
PubMed

Insights

S49076, an inhibitor of MET, AXL, and FGFR, shows dual antitumor activity by targeting MET or Aurora B. This agent enhances radiotherapy efficacy in both MET-dependent and independent tumors, supporting its clinical evaluation with radiation therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • HGF/MET signaling pathway is a target for cancer therapies, particularly in non-small cell lung cancer (NSCLC).
  • Combination therapies involving MET inhibitors and radiotherapy are under investigation, but clinical data are limited.
  • S49076 is an oral inhibitor targeting MET, AXL, and FGFR, currently in Phase I/II trials for NSCLC.

Purpose of the Study:

  • To investigate the impact of S49076 on MET signaling, cell proliferation, and survival.
  • To evaluate the combination of S49076 with radiotherapy in preclinical cancer models.
  • To determine if S49076 has dual antitumor activity and its efficacy in MET-dependent and independent tumors.

Main Methods:

  • Assessed S49076's effects on MET signaling, cell proliferation, and clonogenic survival in various cancer cell lines.
  • Utilized MET-dependent and MET-independent cell lines for in vitro studies.
  • Evaluated the combination of S49076 and radiotherapy in subcutaneous and orthotopic tumor models in vivo.

Main Results:

  • S49076 demonstrated cytotoxic activity against MET-dependent cells via MET inhibition at low doses.
  • S49076 inhibited growth of MET-independent cells by targeting Aurora B at clinically relevant doses.
  • S49076 significantly improved the antitumor efficacy of radiotherapy in both MET-dependent and MET-independent models.

Conclusions:

  • S49076 exhibits dual antitumor activity, acting through MET inhibition or Aurora B targeting.
  • S49076 enhances the efficacy of radiotherapy in a broad range of tumors, irrespective of MET dependency.
  • These findings support the clinical investigation of S49076 in combination with radiation therapy for various cancers.

More Related Videos

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

8.0K
Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells06:29

Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells

Published on: July 30, 2020

3.5K

Related Concept Videos

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
56